Table 3.
High-resolution respirometry findings in animal diabetes studies.
| Animal Model | Tissue Type | Main Effects | Normalization | Ref. |
|---|---|---|---|---|
| C57BL/6J mice | Skeletal muscle (hindlimb muscle) |
Peak respiration by the diabetic mitochondria required a higher level of ADP (right shift in the curve of O2 flux vs. ADP) | Tissue mass | [42] |
| db/db mice bred on a C57BL/6J background | Skeletal muscle (soleus; extensor digitorum longus) |
In soleus muscle: Increased NADH-linked OXPHOS Increased OXPHOS capacity Increased ET capacity Increased succinate-linked ET capacity No change in LEAK respiration No change in L/E coupling control ratio No change in P/E control ratio In extensor digitorum longus muscle: Decreased NADH-linked OXPHOS No change in OXPHOS capacity No change in ET capacity No change in succinate-linked ET capacity Increased LEAK respiration No change in L/E coupling control ratio No change in P/E control ratio |
Tissue mass | [38] |
| C57BL/6J mice (type 1 diabetes and control) C57BL/Ks db/db mice (type 2 diabetes) |
Skeletal muscle (quadriceps femoris; biceps femoris; soleus; gastrocnemius) |
In early-disease type 1 or type 2 diabetes: No change in NADH-linked OXPHOS No change in succinate-linked OXPHOS No change in NADH-linked ET capacity No change in succinate-linked ET capacity |
Tissue mass | [43] |
| ZDF rats non-diabetic fa/+ ZDF rats obese, diabetic, fa/fa |
Skeletal muscle (tibialis anterior) |
No difference in NADH-linked OXPHOS No difference in CII supported respiration Increased RCR dependent on CI substrates No difference in RCR dependent on CII substrates |
Tissue mass Control OXPHOS |
[41] |
| db/db mice bred on a C57BL/6J background | Liver tissue | No change NADH-linked OXPHOS No change in OXPHOS capacity Decreased in ET capacity Decreased succinate-linked ET capacity No change LEAK respiration No change in L/E coupling control ratio Increased in P/E control ratio |
Tissue mass | [38] |
| C57BL/6J mice (type 1 diabetes and control) C57BL/Ks db/db mice (type 2 diabetes) |
Liver tissue |
At the early stage of type 1 diabetes: Increased NADH-linked OXPHOS Increased succinate-linked OXPHOS Increased NADH-linked ET capacity Increased succinate-linked ET capacity At the late stage of type 1 diabetes: No change in NADH-linked OXPHOS No change in succinate-linked OXPHOS No change in NADH-linked ET capacity No change in succinate-linked ET capacity At the early stage of type 2 diabetes: Increased NADH-linked OXPHOS Increased succinate-linked OXPHOS Increased NADH-linked ET capacity Increased succinate-linked ET capacity At the late stage of type 2 diabetes: No change in NADH-linked OXPHOS No change in succinate-linked OXPHOS No change in NADH-linked ET capacity Increased succinate-linked ET capacity |
Tissue mass | [43] |
| IR/IRS-1+/− mice generated by crossing mice heterozygous for insulin receptor null and IRS-1 null alleles, respectively, into the C57BL/6N background |
Liver tissue |
In high fat diet type 2 diabetic mouse model: No change in NADH-linked ROUTINE respiration No change in succinate-linked ROUTINE respiration In insulin-resistant mouse model (without diabetes): No change in NADH-linked ROUTINE respiration Decreased succinate-linked ROUTINE respiration In type 1 diabetic mouse model: Increased in NADH-linked ROUTINE respiration No change in succinate-linked ROUTINE respiration |
Tissue protein | [46] |
| Psammomys obesus | Liver tissue | Decreased NADH-linked ROUTINE respiration Decreased NADH-linked OXPHOS No change in succinate-linked ROUTINE respiration No change in succinate-linked OXPHOS No change in LEAK respiration Decreased RCR |
Tissue protein | [44] |
| C57BLKS/J db/db and db/m mice | Liver tissue | Decreased NADH-linked OXPHOS Decreased succinate-linked OXPHOS Decreased CIV-dependent OXPHOS |
Mitochondrial mass | [45] |
| FVB/N mice | Heart muscle (left ventricle) |
No change in NADH-linked OXPHOS Decreased succinate-linked OXPHOS No change in LEAK respiration |
Tissue mass | [50] |
| Ldlr−/− and C57BL/6J mice | Heart muscle | Increased NADH-linked OXPHOS Increased succinate-linked OXPHOS |
To controls | [49] |
| C57/BL6J mice | Heart muscle | Decreased NADH-linked OXPHOS | Tissue mass mtDNA copy number |
[48] |
| Wistar rats | Heart muscle | Decreased RCR Higher LEAK control ratio Increased P/E control ratio |
No information | [57] |
| Wistar rats | Heart muscle | Decreased NADH-linked OXPHOS Decreased OXPHOS capacity Decreased ET capacity Decreased RCR dependent on CI substrates No difference in RCR dependent on CII substrates |
Tissue mass Citrate synthase |
[54] |
| Wistar rats | Heart muscle | Decreased NADH-linked OXPHOS Decreased OXPHOS capacity Decreased ET capacity |
Volume | [51] |
| C57BL/6 mice | Heart muscle |
At 2 weeks of diabetes: Decreased NADH-linked OXPHOS Decreased succinate-linked OXPHOS Decreased OXPHOS capacity At 10 weeks of diabetes: No changes NADH-linked OXPHOS mediated by glutamate Increased NADH-linked OXPHOS mediated by glutamate and pyruvate No changes succinate-linked OXPHOS No changes OXPHOS capacity |
Mitochondrial protein content | [59] |
| NOD/ShiLtJ mice and NOR/Lt mice | Heart muscle | No changes OXPHOS capacity Decreased LEAK respiration Increased RCR |
Tissue mass | [58] |
| db/+ and db/db C57BL/Ks mice | Heart muscle | Decreased NADH-linked OXPHOS Decreased ET capacity No change in LEAK respiration |
Tissue protein | [53] |
| wild type C57BL/6J mice and CLS mice | Heart muscle | Decreased NADH-linked OXPHOS Decreased OXPHOS capacity No change in LEAK respiration No change NADH-linked OXPHOS No change OXPHOS capacity No change in LEAK respiration |
Tissue protein | [52] |
| Nile rats | Retina homogenate | Decreased FCR for NADH pathway Increased FCR for succinate pathway FCR normalized to OXPHOS capacity |
Tissue mass | [66] |
| TRPC6 global knockout mice and wild type mice | Hippocampal neuron homogenate | Decreased NADH-linked OXPHOS Decreased OXPHOS capacity Decreased ET capacity Decreased succinate-dependent ET capacity Decreased NADH-dependent LEAK respiration |
Tissue mass | [73] |
| Wistar rats | Kidney homogenate | Decreased ROUTINE respiration in the presence of CI substrates No change in ROUTINE respiration in the presence of CII substrate No change in LEAK respiration Decreased RCR dependent on CI substrates No difference in RCR dependent on CII substrates |
Tissue mass | [68] |
| Sprague-Dawley rats | Kidney homogenate | Decreased NADH-linked OXPHOS Decreased OXPHOS capacity No change in RCR Increased LEAK respiration |
Mitochondrial protein content | [69] |